Bilirubin - urine: MedlinePlus Medical Encyclopedia

Hi!
So about two weeks ago, I woke up feeling extremely nauseous. In an attempt to make myself feel better, I made some homemade chicken noodle soup, but after eating I felt ridiculously and uncomfortably full. I assumed I just ate a lot and then went to bed. The next day, I woke up with the same uncomfortable feeling, but I assumed I was just very bloated. My stomach felt extremely heavy to the point where I felt like I had chicken noodle soup in my lungs. I spent the day doing things to help with bloating, but nothing really seemed to help. I called some family members who work in healthcare and one of them asked me if my urine was dark, but it wasn't at that point.
The next day, I woke up and my pee was bright orange, so I was obviously concerned. I waited one more day to be sure, but then decided I should go to the ER. While I was there, they took my blood and urine samples and told me my bilirubin levels were elevated (3.0, conjugated). They thought it was a gallstone but after an ultrasound and a CT scan, they found nothing. They sent me home with some Tylenol and Motrin for the pain and told me to come back if I noticed my eyes turning yellow.
Two days later, the pain was still pretty awful. I couldn't eat anything without feeling horrible nausea and was losing weight like crazy. The few times I was able to eat I would throw it back up. I decided to go to the ER again after vomiting and seeing blood in there, in addition to my eyes looking a little yellow. So I went back to the ER for them to tell me they thought I had a virus, and tested me for mono. It came back negative and my lab results were pretty much the same. They told me to see a GI so I flew home to see one ASAP.
By the time I went to see the GI, the pain was gone and everything was normal except my urine was still dark. GI ordered some more lab tests (which I am going to do tomorrow) and an endoscopy scheduled for December 19th. That was on the 4th of December. Now, my urine is back to a normal color and I feel none of the symptoms. I've been eating normally and have been completely fine.
What I'm wondering is how worried I should be exactly? I feel completely fine, and I'm worried that the tests are going to come back with no information, and I'm just going to have to be doing additional tests which I cannot afford. Is it worth going through with the endoscopy? Was this even a gallbladder attack? I've read that they last from 15minutes to a couple hours, but I had this abdominal pain and jaundice for about a week and a half. Any information would be helpful! Thanks, and sorry for the long read!

Species: Dog
Age: 4
Sex/Neuter status: F/Spayed
Breed: Pitbull
Body weight: 55 lb
History: She started acting lazy and tired. Her eating went down and she started drinking more.
She developed fluid around her lungs, which the vet drained yesterday.
Her liver and spleen are enlarged.
Her Dad died of Immune Mediated Hemolytic Anemia.
Clinical signs: See above
Duration: 4 days
Your general location: Chicago Illinois
Links to test results, X-rays, vet reports etc: Hematology 11/7/17 (Order Received) 11/8/17 1:22 AM (Last Updated) TEST RESULT REFERENCE VALUE
RBC 6.62 5.39 - 8.7 M/µL
Hematocrit 48.4 38.3 - 56.5 %
Hemoglobin 16.3 13.4 - 20.7 g/dL
MCV 73 59 - 76 fL
MCH 24.6 21.9 - 26.1 pg
MCHC 33.7 32.6 - 39.2 g/dL
% Reticulocyte 2.1 %
Reticulocyte 139 10 - 110 K/µL H
Reticulocyte Comment In nonanemic dogs, a reticulocyte count of greater than 110 K/uL of blood may be a transient physiologic response or evidence of bone marrow response to an increased peripheral demand. A persistent reticulocyte count >110 K/uL may indicate occult blood loss, underlying hemolytic disease or disorder that causes an absolute erythrocytosis. Serial monitoring of the erythrogram and reticulocyte count may help determine the significance of this finding. The following chart can be used as a guideline to determine the degree of regenerative response. Degree of bone marrow response (K/uL): Mild 110-150 Moderate 150-300 Marked >300 WBC 13.2 4.9 - 17.6 K/µL
% Neutrophil 78.6 %
% Lymphocyte 11.0 %
% Monocyte 4.5 %
% Eosinophil 5.8 %
% Basophil 0.1 %
Neutrophil 10.375 2.94 - 12.67 K/µL
Lymphocyte 1.452 1.06 - 4.95 K/µL
Monocyte 0.594 0.13 - 1.15 K/µL
Eosinophil 0.766 0.07 - 1.49 K/µL
Basophil a
0.013 0 - 0.1 K/µL
Generated by VetConnect® PLUS November 8, 2017 09:54 AM Page 1 of 4 MUSE PET OWNER: DATE OF RESULT: 11/7/17 LAB ID: 1900844177 Hematology (continued) TEST RESULT REFERENCE VALUE Platelet 420 143 - 448 K/µL a AUTOMATED CBC Chemistry 11/7/17 (Order Received) 11/8/17 1:22 AM (Last Updated) TEST RESULT REFERENCE VALUE Glucose 103 63 - 114 mg/dL
IDEXX SDMA a 13 0 - 14 µg/dL
Creatinine 1.1 0.5 - 1.5 mg/dL
BUN 14 9 - 31 mg/dL
BUN:Creatinine
Ratio 12.7
Phosphorus 5.7 2.5 - 6.1 mg/dL
Calcium 11.2 8.4 - 11.8 mg/dL
Sodium 147 142 - 152 mmol/L
Potassium 5.1 4.0 - 5.4 mmol/L
Na:K Ratio 29 28 - 37
Chloride 109 108 - 119 mmol/L
TCO2
(Bicarbonate)
25 13 - 27 mmol/L
Anion Gap 18 11 - 26 mmol/L
Total Protein 6.0 5.5 - 7.5 g/dL
Albumin 3.0 2.7 - 3.9 g/dL
Globulin 3.0 2.4 - 4.0 g/dL
Alb:Glob Ratio 1.0 0.7 - 1.5
ALT 195 18 - 121 U/L H
AST 101 16 - 55 U/L H
ALP 68 5 - 160 U/L
GGT 6 0 - 13 U/L
Bilirubin - Total 0.3 0.0 - 0.3 mg/dL
Bilirubin - Unconjugated 0.2 0.0 - 0.2 mg/dL
Generated by VetConnect® PLUS November 8, 2017 09:54 AM Page 2 of 4 MUSE PET OWNER: DATE OF RESULT: 11/7/17 LAB ID: 1900844177 Chemistry (continued) TEST RESULT REFERENCE VALUE Bilirubin - Conjugated 0.1 0.0 - 0.1 mg/dL
Cholesterol 157 131 - 345 mg/dL
Creatine Kinase 251 10 - 200 U/L H
Hemolysis Index N b Lipemia Index N c a BOTH SDMA AND CREATININE ARE WITHIN THE REFERENCE INTERVAL which indicates kidney function is likely good. Evaluate a complete urinalysis and confirm there is no other evidence of kidney disease. b Index of N, 1+, 2+ exhibits no significant effect on chemistry values. c Index of N, 1+, 2+ exhibits no significant effect on chemistry values. Urinalysis 11/7/17 (Order Received) 11/8/17 1:22 AM (Last Updated) TEST RESULT REFERENCE VALUE
Collection FREE-CATCH
Color DARK YELLOW
Clarity CLOUDY
Specific Gravity 1.030
pH 5.0
Urine Protein 1+ (100-200 mg/dL) a
Glucose NEGATIVE
Ketones TRACE b
Blood / NEGATIVE
Hemoglobin
Bilirubin 1+
Urobilinogen NORMAL
White Blood 2-5
Cells
0 - 5 HPF
Generated by VetConnect® PLUS November 8, 2017 09:54 AM Page 3 of 4 MUSE PET OWNER: DATE OF RESULT: 11/7/17 LAB ID: 1900844177 Urinalysis (continued) TEST RESULT REFERENCE VALUE
Red Blood Cells 0-2 HPF
Bacteria NONE SEEN
Epithelial Cells RARE (0-1)
Mucus NONE SEEN
Casts NONE SEEN
Crystals 2+ CALCIUM OXALATE DIHYDRATE (6-20)/HPF
a Protein test is performed and confirmed by the sulfosalicylic acid test.
b Detection of trace ketones in patients who are normoglycemic or have negative urine glucose is non-specific and of limited clinical significance.
Endocrinology 11/7/17 (Order Received) 11/8/17 1:22 AM (Last Updated) TEST RESULT REFERENCE VALUE
Total T4 a 1.7 1 - 4 µg/dL
a Interpretive ranges: <1.0 Low 1.0-4.0 Normal

4.0 High 2.1-5.4 Therapeutic

Edited: formatting

As mentioned in the syllabus one aspect of Biochemistry deals with two direct yet deceptively simple questions. These are: (1) where did it come from, and (2) where does it end up?
In this lecture, we will ask these two questions to the hemoglobin-oxygen complex. As we answer these questions, we will touch upon oxygen transport to the cells, the expression and degradation of proteins, and the biosynthesis and breakdown of heme.
In the introductory lecture, we attempted to perform some run-of-the-mill, double-entry accounting. Each time we inhaled, we learned that a certain percentage of oxygen molecules were getting ‘fixed’ inside our body. Let’s pick up from there.
The oxygen we inhale not only dissolves in our blood, but it also binds tightly to a special protein found in our erythrocytes called Hemoglobin. The protein data bank (PDB) contains more than 80,000 structures of proteins, and the following GIF was downloaded from that site. The PDB also has a section called the molecule of the month. In this section, they describe in crisp, atomic detail how some select proteins do what they do. Their section of hemoglobin is linked HERE.
Specifically, one molecule of oxygen binds to a central Iron atom in another molecule called heme. The heme molecule contains 4-pyrrole rings linked by methylenes. Hemoglobin, contains a heme portion, and a protein portion called globin. Oxygen is transported to the tissues by means of this oxygen-hemoglobin complex. Let us pay close attention to the structure of this complex and ask: (1) where did it come from, and (2) where does it end up?
In the case of this particular complex, let us divide the first part into 3 subsections, and ask: (a) where did the oxygen molecule come from, (b) where did the globin protein come from, and (c) where did the heme ring come from? Similarly, we can divide the second question into 3 subsections: (a) where will the oxygen end up, (b) where will the globulin protein end up, and (c) where will the heme ring end up? Let’s address each of these questions one by one:
Oxygen
1 (a): Where did the oxygen come from?

• Oxygen is present in the air we inhale, and most of the oxygen molecules in air come from plants. Specifically, the oxygen molecules come from deep inside a plant’s chloroplast. There, each oxygen molecule is created from two molecules of water by a protein-complex known as the oxygen-generating complex. Inside this complex, the oxygen atoms of two water molecules get hitched together into one oxygen molecule. Prior to this moment, these two water molecules were independent. They may have originated from two very different places. However, after a trip to the chloroplasts, the oxygen atoms of these two water molecules get hitched, and now they must spend their lives together as one oxygen molecule. (Imagine the first water molecule evaporating from the surface of the Pacific Ocean, near Hawaii, 10 months ago; and the second water molecule evaporating from the surface of the Indian Ocean, near the South African coast, two years ago. The two water molecules, then, floated as clouds, until last week when they drizzled-down as rain on our neighborhood park. After working their way through the wet mud, and then up some plant root, they finally reached the oxygen-generating complex of a blade of grass, together. On this blade of grass, the oxygen atoms of these two, formerly independent, water molecules, that originated from two random places on the planet, were hitched together to produce one oxygen molecule. This oxygen molecule was floating in the air until just a few seconds ago. Then, it entered our lungs and was promptly picked up by our hemoglobin).

2 (a): Where will the oxygen end up?

• This answer also requires a story. In the lungs, oxygen molecules do two things: (1) they dissolve into the blood solution, and (2) they bind to hemoglobin. Hemoglobin behaves as an oxygen reserve. If we only relied on the ability of oxygen to dissolve in blood, we would have nowhere near all the oxygen our body needs. The ability of hemoglobin to bind an oxygen molecule, and subsequently release it, allows us to achieve ~70 fold higher concentrations of oxygen. Nitrogen molecules don’t bind hemoglobin very well, but they do dissolve in blood. Carbon monoxide, on the other hand, binds hemoglobin ~200 fold more tightly than oxygen. If carbon monoxide was present in the inhaled air mixture, it would out-compete oxygen for binding to hemoglobin. Carbon monoxide thus leads to some pretty serious problems. Coming back to the complex of oxygen and hemoglobin, we notice that the complex is itself enclosed inside erythrocytes. As the heart beats, blood is pumped through the body, and the erythrocytes that were near the lungs now start flowing away. As these cells flow away, the oxygen molecules start leaving the oxygen-hemoglobin complex, and enter into the blood solution, from where they enter into other cells in the body. In the muscle, oxygen molecules can also bind to myoglobin, a protein like hemoglobin. Eventually, most oxygen molecules find themselves at the edge of the mitochondrial inner membrane, deep inside cells. Up to this stage, the entire transport process, or the journey, of oxygen from our lungs to the edge of the mitochondria can be understood more or less as a physical process. In other words, it can be understood as a series of binding and unbinding events between oxygen molecules, proteins, and the blood. What happens next to the oxygen molecules at the edge of the mitochondrial inner membrane is not a physical transformation but a chemical one. The transformation of oxygen to water will be a topic for discussion in Lecture 2.

Globin
1(b): Where did the globin come from?

• The globin protein was synthesized from DNA by using several different RNA: including ribosomal RNA, transfer RNA, and messenger RNA. Considerable amount of energy was spent to do this. In fact, protein synthesis is one of the most expensive things a cell can do. The information in the globin gene (which is structurally represented by a strand of DNA) was transcribed on to messenger RNA, and then this protein was synthesized, one expensive peptide bond at a time.

2(b): What will happen to the globin?

• Most erythrocytes have a life-span of ~3 months. As the RBC die, the globin protein is broken down to its individual amino acids. Amino acids are considered too valuable to be squandered as fuel by the body, so they are typically re-used. However, under some circumstances, amino acids can also be burned as fuel by involving transamination, the Urea cycle and the TCA cycle.

Heme
1(c): Where did the heme ring come from?

• The heme ring was synthesized in our body by a series of enzymatic transformations from the amino acid glycine and succinyl CoA, a molecule of the TCA cycle. (The TCA cycle is also a topic for later discussion). First, glycine combined with succinyl CoA to generate a product that upon decarboxylation gave δ-Aminolevulinic acid (ALA). Two ALA molecules were then condensed to give porphobilinogen. Subsequently, four porphobilinogens were deaminated give hydroxymethylbilane that cyclized to uroporphyrinogen. The uroporphyrinogen was decarboxylated to coproporphyrinogen, which was subsequently oxidized to protoporphyrin. Heme is obtained once iron adds to protoporphyrin. The biosynthesis of heme is important because we all need heme to bind oxygen. However, another reason why these transformations are important is because their malfunction results in disease. Specifically, improper execution of some of the steps of heme biosynthesis leads to porphyrias (diseases in which the urine exhibits unnatural colors).

2(c): Where will the heme end up?

• When erythrocytes die, the iron atom is stripped-off from heme and recycled. The protoporhyrin is converted into biliverdin, which is then transformed to bilirubin. Bilirubin is not very soluble, and must be conjugated with glucuronic acid to make it more soluble. This conjugate exits the body via the bile. In addition, intestinal bacteria can convert a small portion of conjugated bilirubin to urobilinogen – a molecule excreted in the urine, and a larger portion of conjugated bilirubin into stercobilinogen - a molecule excreted in the stool.

Let’s step back, and take a moment and think about the origin and fate of biomolecules. For the past three months a heme molecule, bound to globin, dutifully brought oxygen from all over the planet, to every cell in our body. It brought oxygen to the muscles of our heart, allowing it to beat. It brought oxygen to the neurons in our brain, contributing to our thoughts. However, very soon this heme molecule will leave our body. Right now, there might also be some spanking new heme molecules binding to oxygen for the first time in their life. And then, in around three months, they too will be out of our body.
This is also a good place to introduce the winner of the 1930 Nobel Prize in Chemistry: Hans Fischer and the Award Speech
Assignment 1: Draw the following structures showing interatomic bonds as lines: You can use a white board and marker, pen/pencil and paper, or use any freely downloadable drawing software.

• (1) Oxygen
• (2) Water
• (3) Carbon Monoxide
• (4) Pyrrole
• (5) Glycine
• (6) Succinic Acid and Succinate
• (7) Glucuronic Acid
• (8) Heme

Assignment 2: Write a short research memo (one or two paragraphs) about any Porphyria using available internet resources.